Method and device for collection of liquid samples

ABSTRACT

Device for collection of liquid samples has a pump (16) for pumping sampling liquid (24), a tube (7) for delivering the sampling liquid, sample container (23) for collection of the sampling liquid, and a transport device for moving the tube in succession from one sample container to the next sample container in at least one row of sample containers. An elastic cloth (22) is sealingly applied over the openings of the sample containers, and a slit (21), in which the tube (7) runs, is arranged in the cloth. The transport device is arranged to stop the tube when it is in a position over the sample container.

The invention refers to a method for collection of liquid samples aswell as a device for carrying out the method according to the invention.More specificially, the invention refers to a method in which a samplingliquid is delivered by means of a pump to a sample container via a tubewhich is moved by a transport device in succession from one samplecontainer to the next sample container in several rows of samplecontainers, the tube after the last sample container in a row beingmoved to the nearest sample container in the next row.

When medicinal samples are taken--as well as in other instances--aperson has to go to the patient or to a place for sampling in order toobtain the necessary sample by means of a canula or some other samplinginstrument. This procedure has to be repeated each time a sample istaken. If kinetic changes are to be followed the sampling has to takeplace with some regularity so that concentration changes with time canbe determined with any relevance in subsequent analyses.

The most usual way to regularly take medicinal samples is that somebodyinserts a canula into the patient and collects a sample of intervals offor with half an hour. The samples are then transported to another placefor analysis, e.g. a laboratory. However, when the results from theanalysis are not of acute significance the analysis of the samples canwait until all the samples have been taken.

Apparatuses for regular sampling of blood are described. Theseapparatuses, built around conventional fraction collectors, are big andcan not easily be carried. The patient must thus remain in the vicinityof the permanently stationed apparatus. Systems are also described inwhich the analysis of the sample takes place continuously. In thesecases the analysis is usually based on the determination of glucose.Such a system is described in U.S. Pat. No. 4,123,353.

In more expensive systems for blood sampling the results from theanalysis are utilized directly, e.g for regulating the dosage ofinsulin. On the other hand, if the results from the analysis are not tobe used until a test series is completed the same information can beobtained if the laboratory analyses all the samples afterwards.Furthermore, if separate samples are collected at a certain samplingseveral different types of analyses can advantageously be performed onthe same sample.

In order to further facilitate a flexible use the apparatus should bedesigned to be portable. However, a simple portable system forcontinuous blood sampling or other kinds of sampling does not exist onthe market. An essential prerequisite for a portable equipment is thatthe liquid samples are not spilled. Furthermore, it is desirable if thesamples, when necessary, can be handled aseptically.

The purpose of the present invention is to facilitate and simplify themethod of regular or continuous sampling above all during blood samplingby using a portable device which gives a low manufacturing cost. Thedevice for collection of liquid samples according to the invention inincludes a special fraction collector which is so constructed that thesamples are not spoiled even if the device is turned sideways or upsidedown.

In order to achieve this purpose the invention has obtained thecharacterizing features of claim 1 and 9.

In order to explain the invention in more detail two embodiments thereofwill be described below reference being made to the accompanyingdrawings in which

FIG. 1 is an overall view of a device according to the invention,

FIG. 2A is a detail view of the device in cross section,

FIG. 2B corresponds to FIG. 2A but shows another cross section whichillustrates another point of the course of sampling,

FIG. 3 is a detail view of the device according to FIG. 1, and

FIG. 4 shows another embodiment of a device according to the invention.

In the overall view of FIG. 1 a sample is sucked out at a samplingpoint 1. The sample can be blood or some other liquid or suspensionwhich is to be analyzed. At the same time as the sample is sucked out itis usually diluted and mixed with a diluent. This preferably takes placein the tip of a double-lumen catheter 4. The diluent is pumped by a pump16 from a container 2 with diluent to the catheter 4 via a tubing 3. Thesame pump 16 is used to pump the mixed sampling liquid 24 via a tubing 5to a tube 7 which ends over a sample container 23 in a fractioncollector in which the sample containers are arranged in parallel rows.In a preferred embodiment of the invention the fraction collector isdesigned with the sample containers arranged in parallel rows butfraction collectors can also be used with the sample containers arrangedin a spiral shaped pathway or the like.

The diluent can contain one or several substances which prevent thecontents from being coagulated or destroyed in other ways. Thesesubstances can also be added to the sample containers in advance in asoluble or solid form. The surface in the tubing 5 can also be coveredwith for example an inhibitor which can either be immobilized or beslowly released into the sampling liquid.

After the sample container 23 has been filled with sampling liquid thetube is moved to the next sample container and so on. When the lastsample container in one row has been filled with sampling liquid thetube is moved to the nearest sample container in the next row in one ofseveral rows of sample containers. The sample containers preferablyconsist of wells in a microtiter plate and the tube 7 is a canula, butother embodiments can also be suitable for specific applications.

In order to prevent the samples from leaking out from the filled samplecontainers these can be covered by a septum which is penetrated by thecanula in every container. This procedure is preferred if it is requiredthat the samples must be handled sterilely. However, an shown in FIG.2A, it is preferred that the containers are covered with an elasticcloth 22 having a slit 21 in which the tube 7 can run. Recesses 25 arearranged in the cloth facing the sample containers 23, the diameter ofwhich preferably being a little smaller than the diameter of the samplecontainers. The recesses are preferably centered exactly over theopenings of the containers. When the tube in the cloth 22 is brought tofollow the slit 21 between two sample containers 23 the tube does notcompletely penetrate the cloth. However, in the recesses 25 over eachsample container, FIG. 2B, the tube reaches so far down within the slitthat the tip of the tube runs free from the elastic cloth. By thisdesign of the elastic cloth it is avoided that sampling liquidpenetrates into the slit when the liquid leaves the tube and that liquidis transferred between the sample containers. If a sterile procedure isnot absolutely necessary this handling of the sample is sufficient.

In this embodiment, a guiding plate 10 of some stiff material isarranged over the elastic cloth 22 for the purpose of guiding the tube 7in the slit 21, above all when turned after the last sample container inone row towards the nearest sample container in the next row. Slots 9are punched in the guiding plate 10 and are located immediately over thecorresponding slits in the cloth. In other applications a devicecorresponding to the guiding plate is arranged at the end of each row ofsample containers.

When turned between rows of sample containers the tube is forced over tothe next row by means of a guiding device. In a preferred embodiment ofthe invention, FIG. 3, the tube 7 is attached in the middle of atriangular guiding sledge 8 which preferably is arranged to slide alongtwo smooth bars 31 arranged perpendicular to the rows of samplecontainers. The sledge can be arranged to elide in other ways, e.g. in agroove on a bar.

The bars are in both ends attached to screw pieces 17 which are forcedforwards or backwards by means of rotating screw bars 13, a toothed belt14 and a motor 12 which operates the screw bars 13 via the toothed belt14. The whole part in which the sledge runs is moved forwards when thetube is moved from one sample container to the next sample container.The position of the sledge is controlled by a revolution counter 18 aswell as an end point and starting point reader 19. The reader registerswhen a portion of the screw piece is immediately opposite the end pointor the starting point. In a preferred embodiment of the invention thereader 19 is used only in the beginning of the sampling, and theremaining control of the position of the tube 7 is handled by arevolution counter 18. The revolution counter registers the number ofrevolutions of the screw bars 13. The rotation of the screw barscorresponds to a displacement of the guiding sledge 8 along the row ofsample containers. By measuring the rotation of the screw bars it ispossible to determine the position of the tube 7 so that it can beguided to be moved between two sample containers in a row. The signalsfrom the revolution counter 18 are also used for changing the directionof the motor 12 at the end of each row of sample containers so that thetube 7 follows a zigzag formed pathway along all the sample containers.

When a row of sample containers, usually 12, have been filled the sledgetogether with its tube is forced over to the next row of samplecontainers either by means of the slots 9 in the guiding plate or bymeans of an inclined deflection bar 11 which facilitates the passage ofthe tube 7 to the next row of sample containers. The passage takes placein such a way that the sledge continues in the same direction after thelast sample container in one row has been filled with sampling liquid.Then at 33 the downward projecting tube 7, and thus the sledge 8, areforced aside by the deflecting slot 9 in the guiding plate 10. However,an inclined deflection bar 11 preferably assists in the passage byforcing aside the triangular sledge 8 in this case. The slot 9 in theunderlying guiding plate 10 is then at 33 arranged to follow the pathwayof the sledge 8 and thus the tube 7, the pathway coincides with theinclined motion the sledge is forced to make. At the same time the tubepasses a flap 15 in the rigid plate 10, which is located approximativelywhere the elastic cloth ends. After this point the slot 9 in the guidingplate passes into an open area.

When the motor 12 operating the part including the sledge changesrotational direction the tube will be forced into the next slot 9 in theguiding plate 10 by the inclined design of the plate above the flap 15.Then the tube is forced into the corresponding slot 21 in the cloth 22.The flap mentioned above thus prevents the tube from returning to theslot from which it came.

FIG. 4 shows a second embodiment for guiding the tube from one samplecontainer to the next sample container, an alternative guiding devicefor transferring the tube 7 from one slit in a row of sample containersto the next slit in the next row of sample containers being shown at thesame time. In this case the tube 7 above the elastic cloth is attachedto an endless band 41 The band runs around turning wheels 44 arranged atthe ends of the rows of sample containers between these In order toensure a proper position for the tube when it discharges liquid to thesample containers the band is preferably easily deflectable laterallybut is non-extensible. The band is pulled from the first samplecontainer in one corner of the sample plate 6 to the last samplecontainer in the diagonal corner by a motor 43 with driving wheels 42.At the passage between two rows of sample containers the band 41 pullsthe tube 7 around the turning wheel 44. In this case the slit in theelastic cloth as well as the slot in the rigid plate runs around theturning wheel 44 to the next row. Since the band 44 provides sufficientsteadiness to the tube 7 the rigid guiding plate can be omitted in thisembodiment of the invention. Nor is a flap required for preventing thetube from returning to the same slit since the tube is advanced in thesame direction. The guiding plate can also be omitted when another typeof pathway is chosen.

In practice, at continuous operation the design of the device accordingto the invention implies a time difference of about 3 minutes from thetime of sampling at the sampling point 1 until the sample is deliveredinto a sample container 23. The sampling pump is working as the samplecontainers are filled, which takes 3 minutes, and the volume from thesampling point 1 to the tube 7 thus corresponds to the volume of onesample container. The pump is stopped when the tube 7 is moved betweenthe containers. If sampling has to take place during a considerableperiod of time the system can be designed electronically so that thesampling takes place more slowly. This means that the pump 16 worksintermittently. If, for example, a sample for one container is to besampled during 10 minutes in stead of 3 minutes the pump works for 6seconds and is idle for 14 seconds, and this sequence is repeated those30 times which are required for filling one container. The sameprocedure is repeated for the remaining containers. The advantage ofthis procedure is that blood corpuscles etc. do not remain stationary inthe tubings for a long continuous period of time and at the same timethe length of tubing from the sampling point 1 to the tube 7 will notbecome critical.

I claim:
 1. Method for collection of liquid samples, wherein thesampling liquid is delivered by means of a pump to a sample containervia a tube which is moved by a transport device in succession from onesample container to the next sample container in at least one row ofsample containers, and the sampling liquid is delivered to the samplecontainers one at a time with the tube positioned over a samplecontainer comprising the step of:providing an elastic cloth which issealingly applied over openings of the sample containers and extendingover the row of sample containers; and bringing the tube to follow apathway in the form of a slit arranged in the cloth, the slit extendingover the openings of the containers along the row of sample containers.2. Method as claimed in claim 1, wherein the tube is brought to stopwhen the mouth of the tube is in a recess in the lower surface of theelastic cloth over a sample container.
 3. Method as claimed in claim 1,wherein the tube is mounted to a carrier which is moved along a guide.4. Method as claimed in claim 1, wherein the tube after the last samplecontainer in a row is guided from this row of sample containers over tothe next row of sample containers by means of a guiding device whenthere are several rows of sample containers.
 5. Method as claimed inclaim 4, wherein the tube when passing from one row to the next row isguided by a guiding plate arranged over the slit.
 6. Method as claimedin claim 4, wherein the tube when passing from one row of samplecontainers to the next row of sample containers is prevented by a flapfrom returning to the previous row of sample containers.
 7. Method asclaimed in claim 1, wherein the tube is carried and imparted movement byan endless band which runs along a plurality of rows of samplecontainers and over turning wheels is passed from one row to the next.8. Device for collection of liquid samples comprising a pump fluidlyconnected to a tube for delivering the sampling liquid, samplecontainers for collection of the sampling liquid arranged in at leastone row, and a transport device for moving the tube in succession fromone sample container to the next sample container along the row ofsample containers, an elastic cloth sealingly applying over openings ofthe sample containers, and a slit formed in the elastic cloth extendingover the openings of the containers along the row of sample containerswherein the tube is movable.
 9. Device as claimed in claimed 8, whereinthe tube is mounted to a carrier which is movably guided on a guidearranged along the slit.
 10. Device as claimed in claim 8, a pluralityof rows of sample containers are arranged, and a guiding device isarranged after the last sample container in a row for guiding the tubefrom this row of sample containers over to the next row of samplecontainers.
 11. Device as claimed in claim 10, wherein the tube isattached to and carried by an endless band which is advanced along aplurality of rows of sample containers and is guided over turning wheelsfrom one row of sample containers to the next row of sample containers.12. Device as claimed in claim 8, wherein a guiding plate is arrangedover the slit, in which a slot is arranged in order to force the tube tofollow a pathway of the slit.
 13. Device as claimed in claim 9, whereinthe guide is perpendicular to the rows of sample containers, and theguide in its ends is attached to means for transportation of the guidealong the rows of sample containers.
 14. Device as claimed in claim 8,wherein a recess is arranged over each sample container in the lowersurface of the elastic cloth.